Tricyclic antidepressants are among the most important drugs in clinical psychiatry. (See the Physicians Desk Reference, 32 Edition, 1978, for disclosure of those tricyclic antidepressants which are in clinical use). The dosage requirements vary considerably among patients. Moreover, numerous published studies have indicated that on identical doses the plasma levels of these drugs can vary 30 fold or more in different patients. Attaining the optimal dose is important in securing maximal therapeutic benefit with minimal side effects. Serious cardiac side effects as well as anticholinergic effects such as dry mouth, difficulty urinating, and interference with eye pressure which could precipitate glaucoma are among the side effects to be avoided. Studies which have measured blood levels by a variety of techniques, most frequently gas chromatography, have indicated that patients show poor therapeutic responses with blood levels which are below the optimal range. See the publications: Ziegler, V. E., et al Arch. Gen. Psychiat. 34:607, 1977; Glassman, A. H., et al. Arch. Gen. Psychiat. 34:197, 1977: Gram, L. F., et al Clin. Pharmacol. Ther. 19:318, 1975; Asberg, M., Clin. Pharmacol. Ther. 16:215, 1974.
Most of the techniques available for tricyclic antidepressants cannot be used readily in routine hospital laboratories. It is generally felt that a simple and sensitive technique to measure these drugs in blood and other body tissues would facilitate the selection of optimal doses.
Presently available techniques are usually only applicable to single drugs. Ideally one would like a technique which can be used with all of the agents.
Clinically employed tricyclic antidepressant drugs have considerable potency in blocking muscarinic cholinergic receptors. See the publication: Snyder, S. H. and Yamamura, H. I. Arch. Gen. Psychiat. 34:236, 1977. Most of these drugs also have considerable potency in blocking histamine H.sub.1 receptors. See the publication: Tran, V. T., Chang, R. S. L. and Snyder, S. H., Proc. Natl. Acad. Sci. USA, 75:6290 1978. The information contained in these above mentioned publications does not provide a tool for measuring amounts of tricyclic antidepressants in body fluids of human patients, because a number of needed elements, all of which were yet to be discovered, had to be discovered to exist for a successful assay for levels of tricyclic antidepressants. It was also necessary to discover the nonspecific effects of body fluids on the binding properties of the muscarinic cholinergic and histamine H.sub.1 receptors and discover means of reducing or abolishing them. It was also necessary to discover that tricyclic antidepressants added to body fluids could be recovered in a form that would still interact with muscarinic cholinergic and histamine H.sub.1 receptors. It was also necessary to show that in the presence of body fluids increasing amounts of tricyclic antidepressants would in a predictable fashion produce a greater blockade of muscarinic cholinergic and histamine H.sub.1 receptors. Only after making a series of discoveries as disclosed herein which reduced nonspecific effects of body fluids on the muscarinic cholinergic and histamine H.sub.1 receptors, permitting recovery of added tricyclic depressant drugs and resulting in reproducible augmentations in receptor blockage with increasing amounts of tricyclic antidepressants in body fluids was it possible to measure tricyclic antidepressants in body fluids with this invention.